title: Follistatin-like 1 suppresses sensory afferent transmission by activating Na+,K+-ATPase.
abstract: Excitatory synaptic transmission is modulated by inhibitory neurotransmitters and neuromodulators. We found that the synaptic transmission of somatic sensory afferents can be rapidly regulated by a presynaptically secreted protein, follistatin-like 1 (FSTL1), which serves as a direct activator of Na(+),K(+)-ATPase (NKA). The FSTL1 protein is highly expressed in small-diameter neurons of the dorsal root ganglion (DRG). It is transported to axon terminals via small translucent vesicles and secreted in both spontaneous and depolarization-induced manners. Biochemical assays showed that FSTL1 binds to the α1 subunit of NKA and elevates NKA activity. Extracellular FSTL1 induced membrane hyperpolarization in cultured cells and inhibited afferent synaptic transmission in spinal cord slices by activating NKA. Genetic deletion of FSTL1 in small DRG neurons of mice resulted in enhanced afferent synaptic transmission and sensory hypersensitivity, which could be reduced by intrathecally applied FSTL1 protein. Thus, FSTL1-dependent activation of NKA regulates the threshold of somatic sensation.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Kai-Cheng
authors.initials: KC
authors.lastname: Li
authors.forename: Fang-Xiong
authors.initials: FX
authors.lastname: Zhang
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Yu
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Zhong
authors.forename: Kai-Hua
authors.initials: KH
authors.lastname: Zhang
authors.forename: Ying-Jin
authors.initials: YJ
authors.lastname: Lu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Ma
authors.forename: Jun-Ru
authors.initials: JR
authors.lastname: Yao
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Wang
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Lin
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
authors.forename: Hua-Sheng
authors.initials: HS
authors.lastname: Xiao
authors.forename: Lan
authors.initials: L
authors.lastname: Bao
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D038702:Follistatin-Related Proteins / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D011984:Sensory Receptor Cells / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D038702:Follistatin-Related Proteins; C448720:Fstl1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase